The purpose of this work is to understand the mechanism by which the vertebrate retinal pigment epithelium phagocytizes and degrades the outer segments of photoreceptor cells, which are continuously sloghed off at their distal ends and synthesized de novo at their proximal ends. A genetic defect prevents phagocytosis of outer segments by the pigment epithelium in one strain of rats with hereditary retinal degeneration, and investigation of the biochemical basis of this defect might help to understand analogous or homologous hereditary retinal degenerations in humans. The projects and experimental approaches currently underway and planned include: 1. characterization of the amounts and relative proportions of hydrolytic enzymes (proteases, phospholipases, glycosidases) present in the lysosome fraction derived from bovine retinal pigment epithelium, using analog substrates, specific inhibitors and purified rod outer segments; 2. isolation and characterization of plasma membrane proteins from retinal pigment epithelium of normal rats and rats with hereditary retinal degeneration; 3. introduction into the subretinal space or into cultured explants of pigment epithelium of liposomes which differ in their phospholipid and/or protein content (with and without opsin); 4. study of the relationship between the phagocytosis of outer segments and the regulation of cGMP metabolism in the retinal pigment epithelium.